Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects

Abstract

Cruzipain (Cz) is the major cystein protease of the protozoan Trypanosoma cruzi, etiological agent of Chagas disease. From a 163-compound dataset, a 2D-classifier capable of identifying Cz inhibitors was obtained and applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. 54 approved drugs were selected as candidates, 4 of which were acquired and tested on Cz and T. cruzi epimastigotes. Among them, the antiparkinsonian and antidiabetic drug bromocriptine and the antiarrhythmic amiodarone showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite.